美国意思协会-CKD指南

Screening,Monitoring,and Treatment of Stage 1to 3Chronic Kidney Disease:A Clinical Practice Guideline From the American College of PhysiciansAmir Qaseem,MD,PhD,MHA;Robert H.Hopkins Jr.,MD;Donna E.Sweet,MD;Melissa Starkey,PhD;and Paul Shekelle,MD,PhD,for the Clinical Guidelines Committee of the American College of Physicians*Description:The American College of Physicians (ACP)developed this guideline to present the evidence and provide clinical recom-mendations on the screening,monitoring,and treatment of adults with stage 1to 3chronic kidney disease.Methods:This guideline is based on a systematic evidence review evaluating the published literature on this topic from 1985through November 2011that was identified by using MEDLINE and the Cochrane Database of Systematic Reviews.Searches were limited to English-language publications.The clinical outcomes evaluated for this guideline included all-cause mortality,cardiovascular mor-tality,myocardial infarction,stroke,chronic heart failure,composite vascular outcomes,composite renal outcomes,end-stage renal dis-ease,quality of life,physical function,and activities of daily living.This guideline grades the evidence and recommendations by using ACP’s clinical practice guidelines grading system.Recommendation 1:ACP recommends against screening for chronic kidney disease in asymptomatic adults without risk factors for chronic kidney disease.(Grade:weak recommendation,low-quality evidence)Recommendation 2:ACP recommends against testing for protein-uria in adults with or without diabetes who are currently taking an angiotensin-converting enzyme inhibitor or an angiotensin II–receptor blocker.(Grade:weak recommendation,low-quality evidence)Recommendation 3:ACP recommends that clinicians select phar-macologic therapy that includes either an angiotensin-converting enzyme inhibitor (moderate-quality evidence)or an angiotensin II–receptor blocker (high-quality evidence)in patients with hyperten-sion and stage 1to 3chronic kidney disease.(Grade:strong recommendation)Recommendation 4:ACP recommends that clinicians choose statin therapy to manage elevated low-density lipoprotein in patients with stage 1to 3chronic kidney disease.(Grade:strong recommenda-tion,moderate-quality evidence)Ann Intern Med.2013;159: For author affiliations,see end of text.This article was published online first at on 22October 2013.Chronic kidney disease (CKD)is nearly always asymp-tomatic in its early stages (1).The most commonly accepted definition of CKD was developed by Kidney Dis-ease:Improving Global Outcomes (KDIGO)(2)and the Kidney Disease Outcomes Quality Initiative (KDOQI)(3)as abnormalities of kidney structure or function,present for more than 3months,with implications for health.Cri-teria for CKD include markers of kidney damage (albu-minuria,as indicated by an albumin excretion rate of 30mg/24h or greater and an albumin–creatinine ratio of 3mg/mmol or greater [Ն30mg/g]);urine sediment abnor-malities;electrolyte and other abnormalities due to tubular disorders;abnormalities detected by histologic examina-tion;structural abnormalities detected by imaging;history of kidney transplantation or presence of kidney damage;or kidney dysfunction that persists for 3or more months,as shown by structural and functional abnormalities (most often based on increased albuminuria,as indicated by a urinary albumin–creatinine ratio of 3mg/mmol or greater[Ն30mg/g])or a glomerular filtration rate (GFR)less than 60mL/min/1.73m 2for 3or more months.Traditionally,CKD is categorized into 5stages that are based on disease severity defined by GFR (3)(Table 1);stages 1to 3are considered to be early-stage CKD.People with early stages of the disease are typically asymptomatic,and the diagnosis is made by using laboratory tests or im-aging.In 2013,KDIGO revised CKD staging to consider both 5stages of GFR as well as 3categories of albuminuria to define CKD severity (2).*This paper,written by Amir Qaseem,MD,PhD,MHA;Robert H.Hopkins Jr.,MD;Donna E.Sweet,MD;Melissa Starkey,PhD;and Paul Shekelle,MD,PhD,was developed for the Clinical Guidelines Committee of the American College of Physicians.Individuals who served on the Clinical Guidelines Committee from initiation of the project until its approval were Paul Shekelle,MD,PhD (Chair );Roger Chou,MD;Molly Cooke,MD;Paul Dallas,MD;Thomas D.Denberg,MD,PhD;Nick Fitterman,MD;Mary Ann Forciea,MD;Robert H.Hopkins Jr.,MD;Linda L.Humphrey,MD,MPH;Tanveer P.Mir,MD;Douglas K.Owens,MD,MS;Holger J.Schu ¨nemann,MD,PhD;Donna E.Sweet,MD;and Timothy Wilt,MD,MPH.Approved by the ACP Board of Regents on 17November 2012.See also:PrintSummary for Patients.......................I-28Web-Only CMEquiz©2013American College of Physicians 835Approximately 11.1%(22.4million)of adults in the United States have stage 1to 3CKD,and prevalence ap-pears to be increasing,especially for stage 3CKD (4,5).Approximately one half of persons with CKD have either stage 1or 2CKD (increased albuminuria with normal GFR),and one half have stage 3CKD (low GFR,with one third of these individuals having increased albuminuria and two thirds having normal albuminuria)(5).The prevalence of CKD is slightly higher in women than in men (12.6%vs.9.7%)(6).Stage 1to 3CKD,reduced GFR,and albuminuria are associated with mortality (7,8),cardiovascular disease (9),fractures (10),bone loss (11),infections (12),cognitive impairment (13),and frailty (14).Treatment of stage 1to 3CKD involves treating associated conditions and compli-cations.Many patients with CKD may already be taking medications targeting comorbid conditions,such as hyper-tension,cardiovascular disease,and diabetes.This American College of Physicians (ACP)guideline presents available evidence on the screening,monitoring,and treatment of stage 1to 3CKD.Clinicians are the target audience.The target patient population for screen-ing is adults,and the target population for treatment it is adults with stage 1to 3CKD.M ETHODSThis guideline is based on a systematic evidence review sponsored by the Agency for Healthcare Research and Quality (AHRQ)(15)and conducted by the Minnesota Evidence-based Practice Center (6)that addressed the fol-lowing key questions:1.In asymptomatic adults with or without recognized risk factors for CKD incidence,progression,or complica-tions,what direct evidence is there that systematic CKD screening improves clinical outcomes?2.What harms result from systematic CKD screening in asymptomatic adults with or without recognized risk factors for CKD incidence,progression,or complications?3.Among adults with CKD stages 1to 3,whether detected by systematic screening or as part of routine care,what direct evidence is there that monitoring for worseningkidney function or kidney damage improves clinical outcomes?4.Among adults with CKD stages 1to 3,whether detected by systematic screening or as part of routine care,what harms result from monitoring for worsening kidney function or kidney damage?5.Among adults with CKD stages 1to 3,whether detected by systematic screening or as part of routine care,what direct evidence is there that treatment improves clin-ical outcomes?6.Among adults with CKD stages 1to 3,whether detected by systematic screening or as part of routine care,what harms result from treatment?The literature search identified randomized,controlled trials and controlled clinical trials published in English from 1985through November 2011,by using MEDLINE and the Cochrane Database of Systematic Reviews and re-view of reference lists of relevant articles and articles sug-gested by experts.Details of the evidence review methods are available in the full AHRQ report (6).This guideline rates the recommendations by using the ACP’s guideline grading system (Table 2)(16).R ISK F ACTORSFORCKDThe major risk factors for CKD include diabetes,hy-pertension,and cardiovascular disease.Other risk factors include older age;obesity;family history;and African American,Native American,or Hispanic ethnicity.Diabe-tes is more prevalent in patients with stage 1to 3CKD (20%)than in patients without CKD (5%)(17).Hyper-tension is also more prevalent in patients with CKD (64%in stage 3and 36%in stage 1)than in patients without CKD (24%)(17).The prevalence of cardiovascular disease increased from 6%in patients without CKD to 36%in those with stage 3CKD (17).S CREENINGFORCKDBenefits of ScreeningDirect EvidenceNo randomized,controlled trials that compared the effect of systematic CKD screening versus no CKD screen-ing on clinical outcomes were identified.Indirect EvidencePrevalence.Among U.S.adults older than 20years,11.1%have stage 1to 3CKD.Approximately 5%of adults younger than 52years and without diabetes,hyper-tension,or obesity have CKD,compared with 68%older than 81years (17).Most patients with stage 1to 3CKD are not clinically recognized to have CKD (18,19).Adverse Health Consequences.Although stage 1to 3CKD is usually asymptomatic,it is associated with mortal-ity (7,8),cardiovascular disease (9),fractures (10),boneCKD Stage Definition1Kidney damage with GFR Ն90mL/min/1.73m 22Kidney damage with GFR of 60–89mL/min/1.73m 23GFR of 30–59mL/min/1.73m 22CKD ϭchronic kidney disease;GFR ϭglomerular filtration rate.*Adapted from reference 3.The Kidney Disease:Improving Global Outcomes Work Group recently updated its definition of CKD progression to include con-sideration of both GFR and albuminuria stages (2).Clinical GuidelineScreening,Monitoring,and Treatment of Stage 1to 3CKD83617December 2013Annals of Internal Medicine Volume 159•Number 12loss(11),infections(12),cognitive impairment(13),and frailty(14).Validity and Reliability of Screening Tests.No popu-lation-based studies have tested the sensitivity or specificity of1-time CKD screening using either estimated GFR or albuminuria or the validity and reliability of repeated screening.Serum creatinine is measured by using a simple blood test.Although no studies have compared GFR esti-mated from serum creatinine values with direct GFR mea-surement,estimation is believed to be reasonably accurate (20).There are many sources of variability when measuring urinary albumin loss(21),and the method of collection and measurement of urinary albumin and creatinine has yet to be standardized.Effect of Treatments on Screen-Detected CKD.There was no randomized trial evidence evaluating the effective-ness of treatment on clinical outcomes of CKD identifiedthrough screening.Harms of ScreeningDirect EvidenceNo randomized,controlled trials have evaluated the harms of systematic CKD screening.Indirect EvidenceExpert opinion suggests that the harms of CKD screening include misclassification of patients owing to false-positive test results,adverse effects of unnecessary test-ing,psychological effects of being labeled with CKD,ad-verse events associated with pharmacologic treatment changes after CKD diagnosis,and possiblefinancial rami-fications of CKD diagnosis.M ONITORING FOR CKDBenefits of MonitoringDirect EvidenceNo randomized,controlled trials have evaluated clini-cal outcomes for patients with stage1to3CKD who were systematically monitored for worsening kidney function versus no CKD monitoring,usual care,or an alternative CKD monitoring regimen.Indirect EvidenceFrequency of Worsening of Kidney Function or Damage in Patients With Stage1to3CKD.The mean annual GFR decline in patients with CKD varies widely,ranging from approximately1to greater than10mL/min/1.73m2(3). Annual rates of conversion from microalbuminuria to macro-albuminuria range from2.8%to9%(22–27).Factors that have been shown to predict faster decline in GFR include diabetes,proteinuria,hypertension,older age,obesity,dys-lipidemia,smoking,male sex,and cause of primary kidney disease.Association of CKD Progression With Adverse Health Consequences.No studies longitudinally assessed the risk for adverse health outcomes in patients with worsening CKD.A meta-analysis of prospective cohort studies reported risk for all-cause and cardiovascular mortality for different GFRs and degrees of albuminuria(8).Patients with albu-minuria and GFR greater than60mL/min/1.73m2(CKD stage1or2)had a higher mortality risk if they had mac-roalbuminuria compared with microalbuminuria,although lower GFR within this range was not associated with a higher mortality risk.Mortality risk was increased in pa-tients with a GFR of45to59mL/min/1.73m2,higher in those with GFR30to44mL/min/1.73m2,and even higher in those with GFR less than30mL/min/1.73m2.Validity and Reliability of Tests to Monitor CKD Progression.The same tests are used both to screen for CKD and monitor its progression.No studies assessed the accuracy,precision,specificity,or sensitivity of estimating GFR over time or for detecting a change in CKD stage on the basis of GFR category.The lack of consistent repro-ducibility in albuminuria measurements causes concern about the ability of longitudinal albuminuria measure-ments to accurately represent CKD progression.Effect of Treatments on Clinical Outcomes in Patients Whose CKD Has Progressed.Evidence is lacking on whether treatments reduce the risk for adverse clinical out-comes in patients with worsening CKD.Harms of MonitoringDirect EvidenceNo randomized,controlled trials were identified that compared the adverse effects of systematic monitoring of stage1to3CKD versus no CKD monitoring,usual care, or an alternative CKD monitoring regimen.Indirect EvidenceExpert opinion suggests that the harms of monitoring for CKD progression include incorrect reclassification of patients,adverse effects of unnecessary testing,labeling ef-fects,adverse events associated with changes in pharmaco-logic treatments after testing,and possiblefinancial rami-fications of a more advanced CKD diagnosis.*Adopted from the classification developed by the GRADE(Grading of Recom-mendations,Assessment,Development,and Evaluation)workgroup.Clinical GuidelineScreening,Monitoring,and Treatment of Stage1to3CKD17December2013Annals of Internal Medicine Volume159•Number12837T REATMENT OF CKDTable3summarizes the evidence on treatments for stage1to3CKD.Antihypertensive DrugsMonotherapyPatients receiving␤-blockers or calcium-channel blockers for CKD treatment may have received other con-comitant antihypertensive agents.Angiotensin-Converting Enzyme Inhibitors Versus Place-bo.Nineteen studies compared treatment with angiotensin-converting enzyme(ACE)inhibitors with placebo in patients with stage1to3CKD(23–26,28–42). Moderate-quality evidence showed that treatment with ACE inhibitors reduced the risk for end-stage renal disease (ESRD)(relative risk[RR],0.65[95%CI,0.49to0.88]) compared with placebo in patients with stage1to3CKD (26–28,31,33–35,38).The risk for ESRD was not re-duced in patients with only microalbuminuria or impaired GFR.Moderate-quality evidence showed that treatment with ACE inhibitors did not reduce the risk for all-cause mortality compared with placebo(23–26,28–39,41)(Ta-ble3).Pooled data from10trials(23–26,29–31,35,36, 39)showed that mortality risk was reduced in patients with microalbuminuria(RR,0.79[CI,0.66to0.96]),although most of the data were derived from a large study that showed no difference in mortality between patients with and without microalbuminuria(43).Therapy with ACE inhibitors did not reduce the risk for cardiovascular mor-tality,myocardial infarction(MI),stroke,or other vascular outcomes.ACE Inhibitors Versus␤-Blockers.Low-quality evi-dence showed no difference in the risk for ESRD or all-cause mortality,cardiovascular mortality,stroke,or heart failure between patients treated with ACE inhibitor mono-therapy compared with␤-blocker monotherapy(44–46) (Table3).ACE Inhibitors Versus Diuretics.Low-quality evidence showed no difference between ACE inhibitor–treated and diuretic-treated patients in terms of risk for ESRD(47) (Table3).Evidence was insufficient evidence to determine whether the treatments alter the all-cause mortality risk. There was no statistically significant difference between the 2treatments in risk for stroke or multiple composite car-diovascular outcomes.ACE Inhibitors Versus Angiotensin II–Receptor Blockers.End-stage renal disease outcomes were not re-ported in studies comparing ACE inhibitor monotherapy with angiotensin II–receptor blocker(ARB)monotherapy. Low-quality evidence showed that there was no difference between these2monotherapies in risk for all-cause mor-tality(36,48–51)(Table3).There was no statistically significant difference between the2treatments for other reported clinical vascular or renal outcomes.ACE Inhibitors Versus Calcium-Channel Blockers.Low-quality evidence showed that there was no difference in the risk for ESRD(47,52,53)or all-cause mortality(23,52–56)between ACE inhibitor monotherapy and calcium-channel blocker monotherapy(Table3).There was also no difference between the2treatments in terms of risk for cardiovascular mortality,stroke,congestive heart failure (CHF),or any composite vascular end point.ACE Inhibitors Versus Non–ACE Inhibitor Antihyper-tensive Therapy.Low-quality evidence showed that ACE inhibitor monotherapy did not statistically significantly re-duce the risk for ESRD compared with non–ACE inhibi-tor antihypertensive therapy(calcium antagonists,␤-blockers,or␣-adrenoblockers)(57)(Table3).Evidence was insufficient that ACE inhibitor therapy compared with non–ACE inhibitor antihypertensive therapy is associated with a reduced risk for all-cause mortality.ARB Monotherapy Versus Placebo.High-quality evi-dence showed that treatment with ARBs reduced the risk for ESRD in patients with stage1to3CKD(RR,0.77 [CI,0.66to0.90])compared with placebo(58–60).How-ever,it was not possible to determine whether risk was also reduced in patients with microalbuminuria or impaired GFR who do not have diabetes and hypertension(58–60). High-quality evidence showed that treatment with ARBs did not reduce the risk for all-cause mortality compared with placebo(58–61)(Table3).Treatment with ARBs did not reduce the risk for cardiovascular mortality,MI, CHF complications,or any other clinical vascular outcome compared with placebo;however,ARB treatment did sta-tistically significantly improve renal outcomes.ARBs Versus Calcium-Channel Blockers.Low-quality evidence showed that ARB monotherapy did not reduce the risk for ESRD(59)or all-cause mortality(59,62)com-pared with calcium-channel blocker monotherapy(Table 3).There was also no statistically significant difference be-tween the2treatments in terms of risk for stroke,cardio-vascular mortality,CHF,or composite vascular end points.␤-Blockers Monotherapy Versus Placebo.End-stage re-nal disease outcomes were not reported in studies compar-ing␤-blocker monotherapy with placebo.Moderate-quality evidence showed that treatment of CKD with a ␤-blocker reduced the risk for all-cause mortality com-pared with placebo(RR,0.73[CI,0.65to0.82])(63–66).␤-Blocker treatment also statistically significantly reduced the risk for cardiovascular mortality(64,66),CHF hospi-talization(65,66),and CHF death(65,66).Calcium-Channel Blockers Versus Placebo.Low-quality evidence showed that treatment with calcium-channel blockers in mostly hypertensive patients with albuminuria did not reduce the risk for ESRD(59)or all-cause mortal-ity(23,59)compared with placebo,although this treat-ment did reduce the risk for MI(23,59)(Table3).There was no statistically significant reduction in composite renal outcomes.Calcium-Channel Blockers Versus␤-Blockers.Low-quality evidence showed that calcium-channel blocker monotherapy did not statistically significantly reduce theClinical Guideline Screening,Monitoring,and Treatment of Stage1to3CKD83817December2013Annals of Internal Medicine Volume159•InterventionOutcomeStrength of Evidence From RCTs (Reference)ResultOther OutcomesAdverse Events*ACE inhibitor vs.placebo MortalityModerate (23–26,28–39,41,42)No reduced risk overall (RR,0.91[95%CI,0.79to 1.05])Reduced risk for composite renal outcomes;mortality risk reduced in patients with microalbuminuria CoughESRDModerate (26–28,31,33–35,38)Reduced risk (RR,0.65[CI,0.49to 0.88])ARB vs.placeboMortality High (58–61)No reduced risk (RR,1.04[CI,0.92to 1.18])Reduced risk for CHF hospitalization (1of 2trials reporting)and composite renaloutcomes (1of 3trials reporting)HyperkalemiaESRDHigh (58–61)Reduced risk (RR,0.77[CI,0.6to 0.90])ACE inhibitor vs.ARB Mortality Low (36,48–51)No reduced risk (RR,1.04[CI,0.37to 2.95])No reduced risk for other outcomes reported NRESRD InsufficientNAACE inhibitor ϩARB vs.ACE inhibitorMortality Moderate (50,71,72)No reduced risk (RR,1.03[CI,0.91to 1.18])Reduced risk for composite vascular outcomesIncreased risk for cough,hyperkalemia,hypotension,and acute kidney failure requiring dialysis ESRDLow (70)No reduced risk (RR,1.00[CI,0.15to 6.79])ACE inhibitor ϩARB vs.ARBMortality Moderate†(60)No reduced risk (RR,1.02[CI,0.93to 1.13])Reduced risk for composite vascular outcomesNRESRDLow†(60)No reduced risk (RR,1.19[CI,0.77to 1.85])␤-Blocker vs.placebo Mortality Moderate (63–66)Reduced risk (RR,0.73[CI,0.65to 0.82])Reduced risk for CVD mortality,CHFhospitalization,CHF death,and composite vascular outcomes Heart failure,fatigue,bradycardia,dizziness,and hypotensionESRDInsufficientNACalcium-channel blocker vs.placeboMortality Low (23,59)No reduced risk (RR,0.90[CI,0.69to 1.19])Reduced risk for MIHyperkalemiaESRDLow (59)No reduced risk (RR,1.03[CI,0.81to 1.32])Thiazide diuretic vs.placebo Mortality Low (69)No reduced risk (RR,1.17[CI,0.74to 1.85])Reduced risk for stroke NRESRD InsufficientNACalcium-channel blocker vs.␤-blockerMortality Low (46,67,68)No reduced risk (RR,0.62[CI,0.31to 1.22])No reduced risk for other outcomes reportedNRESRDLow (46,67)No reduced risk (RR,1.00[CI,0.70to 1.44])Calcium-channel blocker vs.diuretic Mortality Insufficient NANo reduced risk for other outcomes reported NRESRD Low (47)No reduced risk (RR,0.90[CI,0.67to 1.21])Strict vs.standard blood pressure controlMortality Low (46,75,76,78)No reduced risk (RR,0.86[CI,0.68to 1.09])No reduced risk for other outcomes reportedNRESRDLow (46,75,78)No reduced risk (RR,1.03[CI,0.77to 1.38])Statin vs.control Mortality High (29,79,81–87)Reduced risk (RR,0.81[CI,0.71to 0.94])Reduced risk for MI,stroke,most composite vascular outcomes reportedNRESRDLow (79,80)No reduced risk (RR,0.98[CI,0.62to 1.56])Low-protein diet ual-protein dietMortality Low (93–96)No reduced risk (RR,0.58[CI,0.29to 1.16])Reduced risk for composite renal outcome (1trial reporting)Weight loss,weight gain,hyperkalemiaESRDLow (92–94)No reduced risk (RR,1.62[CI,0.62to 4.21])Strict ual glycemic Mortality Insufficient NA No reduced risk for other NR ACE ϭangiotensin-converting enzyme;ARB ϭangiotensin II–receptor blocker;CHF ϭcongestive heart failure;CKD ϭchronic kidney disease;CVD ϭcardiovascular disease;ESRD ϭend-stage renal disease;MI ϭmyocardial infarction;NA ϭnot applicable;NR ϭnot reported;RCT ϭrandomized,controlled trial;RR ϭrelative risk.*Adverse events were sparsely reported in the trials included in this study and often similar in control and treatment groups.†Data derived from a study comparing ACE inhibitor plus ARB combination therapy with either ARB or ACE inhibitor monotherapy.Clinical GuidelineScreening,Monitoring,and Treatment of Stage 1to 3CKD 17December 2013Annals of Internal Medicine Volume 159•Number 12839risk for ESRD(46,67)or all-cause mortality(46,67,68) compared with␤-blocker monotherapy(Table3).No sta-tistically significant difference in renal outcomes was reported.Calcium-Channel Blockers Versus Diuretics.Low-quality evidence showed that calcium-channel blocker monotherapy did not statistically significantly reduce the risk for ESRD compared with diuretic monotherapy(47) (Table3).Mortality data were not reported.There were no statistically significant differences in renal or vascular outcomes reported.Thiazide Diuretics Versus Placebo.No renal outcomes were reported for the comparison of thiazide diuretic monotherapy with placebo.Low-quality evidence showed no difference between the2groups in risk for all-cause mortality(69)(Table3).Diuretic monotherapy statisti-cally significantly reduced the risk for stroke and1com-posite vascular outcome.Combination Therapy Versus MonotherapyACE Inhibitors Plus ARBs Versus ACE Inhibitors Alone.Low-quality evidence showed no statistically sig-nificant difference in risk for ESRD between treatment with ACE inhibitors plus ARBs compared with ACE in-hibitors alone(70)(Table3).Moderate-quality evidence also showed no statistically significant difference in the risk for all-cause mortality in the combined treatment group compared with monotherapy(50,71,72)(Table3).ACE Inhibitors Plus ARBs Versus ARBs Alone.There was no evidence directly comparing the risk for ESRD or mortality with ACE inhibitors plus ARBs compared with ARB monotherapy.However,1trial(60)compared ACE inhibitor plus ARB combination therapy with either ARB or ACE inhibitor monotherapy(results for monotherapy reported together);moderate-quality evidence showed no reduced risk for ESRD,and low-quality evidence showed no reduced risk for all-cause mortality in the combined treatment group(Table3).Other Comparisons.Evidence was insufficient to de-termine the effect of the following comparisons on ESRD or mortality:ACE inhibitors plus calcium-channel blockers versus ACE inhibitor monotherapy or calcium-channel blocker monotherapy;ACE inhibitors plus diuretics versus ACE inhibitor monotherapy;and ACE inhibitors plus di-uretics versus placebo.Combination Therapy Versus Combination TherapyEvidence was insufficient to determine the effect of the following comparisons on ESRD or mortality:ACE inhib-itor plus ARB versus ACE inhibitor plus aldosterone an-tagonist;ACE inhibitor plus diuretic versus ACE inhibitor plus calcium-channel blocker;ACE inhibitor plus aldoste-rone antagonist versus ACE inhibitor plus placebo;and ACE inhibitor and ARB plus aldosterone antagonist versus ACE inhibitor and ARB plus placebo.Strict Versus Standard Blood Pressure ControlSeven studies(46,73–78)randomly assigned patients with stage1to3CKD(mostly with hypertension)to strict versus standard blood pressure targets,and medications varied among studies.The mean achieved blood pressure ranged from128to133mm Hg systolic and75to81mm Hg diastolic in the strict-control group versus134to141 mm Hg systolic and81to87mm Hg diastolic in the standard-control group.Low-quality evidence showed no difference in risk for ESRD(46,75,78)or all-cause mor-tality(46,75,77,78).between strict and standard blood pressure control(Table3).There was no statistically sig-nificant difference between other reported vascular or renal outcomes.Non–Blood Pressure Control InterventionsStatins Versus ControlLow-quality evidence showed that treatment with statins(3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)did not reduce the risk for ESRD in patients with dyslipidemia and stage1to3CKD(79,80)(Table 3).Moderate-quality evidence(subgroup analyses)showed that statins reduced the risk for all-cause mortality in pa-tients with dyslipidemia as well as stage1to3CKD(RR, 0.81[CI,0.71to0.94])(29,79,81–87).Statins were found to statistically significantly reduce the risk for MI, stroke,and most composite vascular outcomes reported.Low-quality evidence from1trial(88)that reported on mortality in patients with CKD and dyslipidemia treated with high-dose atorvastatin(80mg/d)versus low-dose atorvastatin(10mg/d)found no difference in the risk for all-cause mortality(7.0%vs.7.5%,respectively;RR 0.93[CI,0.72to1.20]);however,the high-dose atorvasta-tin group had a decreased risk for CHF hospitalization and composite vascular outcomes.Another study(89)reported no differences between high-and low-dose statin treatment in terms of composite vascular outcomes.No results were reported for ESRD or any renal outcomes.Gemfibrozil Versus Placebo or ControlLow-quality evidence from a single trial(90)supports no difference in all-cause mortality reduction for treatment with the triglyceride-lowering medication gemfibrozil com-pared with placebo(RR,0.91[CI,0.52to1.62]).No individuals in the study experienced ESRD.Gemfibrozil was found to statistically significantly reduce the risk for the composite outcome of fatal coronary heart disease, nonfatal MI,or stroke compared with placebo.Evidence was insufficient to determine whether treatment with gem-fibrozil reduced the risk for ESRD or all-cause mortality compared with a triglyceride-lowering diet(91).Low-Protein Diet Versus Usual-Protein DietLow-quality evidence from3trials comparing a low-protein diet with usual diet in patients with stage1to3 CKD(92–94)showed no statistically significant differenceClinical Guideline Screening,Monitoring,and Treatment of Stage1to3CKD84017December2013Annals of Internal Medicine Volume159•。